{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Noeske J"],"funding":["NIGMS NIH HHS"],"pagination":["5269-79"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4135883"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["58(9)"],"pubmed_abstract":["Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli 70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation."],"journal":["Antimicrobial agents and chemotherapy"],"pubmed_title":["Synergy of streptogramin antibiotics occurs independently of their effects on translation."],"pmcid":["PMC4135883"],"funding_grant_id":["R01 GM105404","R01GM105404","R01-GM65050","R01 GM065050"],"pubmed_authors":["Giacobbe RA","Zambrowski M","Huang J","Cate JH","Olivier NB","Noeske J"],"additional_accession":[]},"is_claimable":false,"name":"Synergy of streptogramin antibiotics occurs independently of their effects on translation.","description":"Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli 70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Sep","modification":"2025-04-22T00:59:15.302Z","creation":"2019-03-27T01:34:14Z"},"accession":"S-EPMC4135883","cross_references":{"pubmed":["24957822"],"doi":["10.1128/aac.03389-14","10.1128/AAC.03389-14"]}}